Cavitand Zn(II)-porphyrin capsules with high affinities for pyridines and N-methylimidazole

Article abstract of DOI:10.1021/jo010107k

Covalent cavitand Zn(II)-porphyrins 17-20 were prepared via multistep syntheses. These host molecules show moderate to excellent binding affinities to N-methylimidazole and pyridine guests. The complexing behavior strongly depends on the spacer's length,

Full text of DOI:10.1021/jo010107k

3998
J . Org. Chem. 2001, 66, 3998-4005
Ca vita n d Zn (II)-P or p h yr in Ca p su les w ith High Affin ities for
P yr id in es a n d N-Meth ylim id a zole
Oskar Middel, Willem Verboom,* and David N. Reinhoudt*
Laboratory of Supramolecular Chemistry and Technology, MESA+ Research Institute,
University of Twente, P.O. Box 217, NL-7500 AE Enschede, The Netherlands
smct@ct.utwente.nl
Received J anuary 26, 2001
Covalent cavitand Zn(II)-porphyrins 17-20 were prepared via multistep syntheses. These host
molecules show moderate to excellent binding affinities to N-methylimidazole and pyridine guests.
The complexing behavior strongly depends on the spacer’s length, number, and rigidity, in addition
to the guest size. Cavitand capping and strapping of porphyrins strongly influence the complex
formation and result in a 10-700-fold enhancement of the binding strength compared to tetraphenyl
Zn(II)-porphyrin.
In tr od u ction
erocycles approximately 10-103 times stronger than
unsubstituted porphyrins, reflecting the shielding effect
of the calix[4]arene moieties; for picoline and N-meth-
ylimidazole K values >106 M-1 in CDCl3 were found. In
the literature a few other calix[4]arene-porphyrin as-
semblies are known. A calix[4]arene was used to cap an
Fe(III)-porphyrin resulting in an excellent oxygen car-
rier in membranes11 and a calix[4]arene was coupled to
a porphyrin using the porphyrin as a fluorescent probe
for monitoring the binding of organic guests in the calix-
[4]arene.12
A cavitand has a completely rigidified and defined
cavity, and a strong enhancement of the binding proper-
ties of the Zn(II)-porphyrin is therefore expected when
the cavitand functions as a porphyrin cap. This paper
describes the first cavitand-capped and -strapped por-
phyrins together with a systematic study on the shielding
effect of the cavitand related to the number, flexibility,
and length of the spacers. This is expressed in a very
strong enhancement of the binding of N-methylimidazole
and pyridine guests compared to the binding to TPP(Zn).
Porphyrins are of biological importance and therefore
widely used in supramolecular chemistry in order to
mimic porphyrin-containing active sites of proteins and
enzymes.1 Fenced, strapped, and a few capped porphyrins
show that a hydrophobic pocket on top of the metal-
containing porphyrin platform enhances the coordination
of electron-donating ligands to the metal center.2 The
capability of the hydrophobic pocket of the capped,
strapped, and fenced Zn(II)-porphyrins to stabilize the
axial binding of ligands is commonly studied by compari-
son with tetraphenylporphyrin(Zn) (TPP(Zn)).3
A number of porphyrin-containing receptors has been
published in the literature during the past two decades.
Different host molecules such as cyclodextrins,4 crown
ethers,5 and calix[4]arenes6 have been used to bridge or
cap a porphyrin. In addition to the Zn(II)-porphyrin
trimer reported by Sanders et al.,7 there are a few
Zn(II)-porphyrin-containing receptors that bind axial
guests in organic solvents with an association constant
of >106 M-1. The capped porphyrins reported by Nolte
et al.8 and Uemori et al.9 show binding of axial guests
with an association constant up to 107 M-1 in CDCl3. As
part of our work to build receptors via a combination of
simple building blocks,10 we have reported a calix[4]arene
doubly strapped porphyrin.6 The receptor binds N-het-
Resu lts a n d Discu ssion
Syn th esis. The capped and strapped porphyrins were
synthesized starting from cavitand tetraamine 113 and
diamine 2,14 respectively (Scheme 1). Reaction of the
amines with either chloroacetyl chloride or 6-bromohex-
anoic acid chloride gave the corresponding di- (3, 4) and
tetraamides (5, 6) in excellent yields (>93%), whereupon
the corresponding aldehydes 7-10 were prepared via a
Williamson ether synthesis by reacting amides 3-6 with
salicylaldehyde. The dialdehydes 7 and 8 were converted
to the corresponding bis(di-2-pyrrolylmethyl) precursors
11 and 12 by adding 10 mol % of trifluoroacetic acid to a
solution of 7 and 8 in pyrrole, respectively.
(1) (a) Lehn, J .-M. Science 1985, 227, 849. (b) Collman, J . P.; Zhang,
X.; Lee, V. L.; Uffelman, E. S.; Brauman, J . I. Science 1993, 261, 1405.
(2) Feiters, M. C. In Comprehensive Supramolecular Chemistry;
Atwood, J . L., Davies, J . E. D., MacNicol, D. D., Vo¨gtle, F., Reinhoudt,
D. N., Lehn, J .-M., Eds.; Elsevier Science Ltd. Pergamon: Elmsford,
1996; Vol. 10, pp 267-360.
(3) Stryer, L. Biochemistry, 3rd ed.; W. H. Freeman and Co.: New
York, 1988; Chapter 7.
(4) Kuroda, Y.; Ito, M.; Sera, T.; Ogoshi, H. J . Am. Chem. Soc. 1993,
115, 7003.
(5) Gunter, M. J .; J eynes, T. P.; J ohnston, M. R.; Turner, P.; Chen,
Z. J . Chem. Soc., Perkin Trans. 1 1998, 1945.
(6) Rudkevich, D. M.; Verboom, W.; Reinhoudt, D. N. J . Org. Chem.
1995, 60, 6585.
(7) Vidal-Ferran, A.; Mu¨ller, C. M.; Sanders, J . K. M. J . Chem. Soc.,
Chem. Commun. 1994, 2657.
(10) Higler, I.; Timmerman, P.; Verboom, W.; Reinhoudt, D. N. Eur.
J . Org. Chem. 1998, 2689.
(11) Kobayashi, N.; Mizuno, K.; Osa, T. Inorg. Chim. Acta 1994, 224,
1.
(8) Elemans, J . A. A. W.; Claase, M. B.; Aarts, P. P. M.; Rowan, A.
E.; Schenning, A. P. H. J .; Nolte, R. J . M. J . Org. Chem. 1999, 64,
7009.
(9) Imai, H.; Munakata, H.; Takahashi, A.; Nakagawa, S.; Ihara,
Y.; Uemori, Y.J . Chem. Soc., Perkin Trans. 2 1999, 2565.
(12) Milbrandt, R.; Weiss, J . Tetrahedron Lett. 1995, 36, 2999.
(13) Boerrigter, H.; Verboom, W.; Reinhoudt, D. N. J . Org. Chem.
1997, 62, 7148.
(14) Boerrigter, H.; Verboom, W.; Van Hummel, G. J .; Harkema,
S.; Reinhoudt, D. N. Tetrahedron Lett. 1996, 37, 5167.
10.1021/jo010107k CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/09/2001

Covalent Cavitand Zn(II)-Porphyrin Capsules
J . Org. Chem., Vol. 66, No. 11, 2001 3999
Sch em e 1
Ch a r t 1
The capped (2H)-porphyrins 13-16 were easily identi-
fied by the signals of the porphyrin-core hydrogen atoms
1
resonating around δ -2.8 in the H NMR spectra and by
the molecular ion peak in the positive FAB mass spectra.
They could not be obtained analytically pure after column
chromatography due to their slight instability. Treatment
of the capped (2H)-porphyrins 13-16 with a large excess
of Zn(OAc)2 afforded the stable cavitand Zn(II)-porphy-
rins 17-20 which could easily be purified by flash column
chromatography.18 The overall yields for 17-20 of the
last two reaction steps, the porphyrin syntheses and the
subsequent insertion of the Zn(II) center, were 0.9%, 6%,
3%, and 5%, respectively.
NMR An a lysis. Structural proof for the cavitand
Zn(II)-porphyrins 17-20 was obtained by several
NMR techniques. The 1H NMR spectrum of capped
Zn(II)-porphyrin 18 (Figure 1) clearly shows its C-4
symmetry. The assignment of the signals originating
from the flexible pentylamido-N-methylene spacers was
accomplished by combining the COSY and TOCSY NMR
spectra. The middle three methylene groups have shifted
(about 1.0 ppm) to an upfield position due to the porphy-
rin’s ring current; two of the methylene groups are reso-
nating at around δ 0.7, the other (closest to the porphy-
rin) at δ 0.9. The OCH2 methylene group is just outside
the ring current since it is residing as a triplet at δ 3.74.
The introduction of short amide-containing spacers
rigidifies the cavitand-porphyrin system for 17 and 19.
The conversion of tetraaldehydes 9 and 10 and dipyr-
romethanes 11 and 12 to capped porphyrins 13 and 14
and strapped porphyrins 15 and 16 was accomplished
in yields comparable to those of other systems reported
and proved to be strongly dependent on the synthetic
methods applied. The conversion of 9 to capped porphyrin
13 could only be accomplished by using the Adler
conditions;15 other methods showed no porphyrin forma-
tion. Only when applying the Lindsey equilibrium condi-
tions,16 using BF3 as the catalyst, could capped porphyrin
14 be obtained. The best results for strapped porphyrins
15 and 16 were obtained via the Lindsey method16 via
TFA and BF3 catalysis, respectively (Chart 1).17
(15) Adler, A. D.; Longo, F. R.; Finarelli, J . D.; Goldmacher, J .;
Assour, J .; Korsakoff, L. J . Org. Chem. 1967, 32, 476.
(16) Lindsey, J . S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.;
Marguerettaz, A. M. J . Org. Chem. 1987, 52, 827.
(17) We have chosen ball-and-stick model representations for the
cavitand Zn(II)-porphyrins instead of, e.g., Isis-draw pictures for
clarity.
(18) The purity of capped Zn(II)-porphyrin 18 follows from the 1H
NMR spectrum (Figure 1).

4000 J . Org. Chem., Vol. 66, No. 11, 2001
Middel et al.
F igu r e 1. 1H NMR spectrum of 18 in CDCl3.
The distance between the cavitand cap and the porphyrin
will be fixed and is contrasting the structural flexibility
in 18. Slow rotation of the short linker groups results in
an 1H NMR spectrum consisting of broadened multiple
signals for, e.g., the spacers and methylenedioxy bridges,19
and the expected C4 symmetry of 17 and the C2 sym-
metry of 19 is lost. COSY and NOESY spectra only show
the expected contacts for the cavitand and porphyrin part
of the molecule and in particular between the Hin and
Hout multiplet regions for the hydrogen atoms of the
methylenedioxy bridges and between the different mul-
tiplet regions residing from the hydrogen atoms of the
spacer.
Strapped porphyrin 20 exhibits a complex 1H NMR
spectrum in CD2Cl2. The aryl substituents of the por-
phyrin reside as two multiplet regions between δ 7.4 and
7.8. Furthermore, many of the signals are doubled or
broadened. A clear contact in the ROESY NMR spectrum
was found between the resonances of the OCHinO and
the resonance of one hydrogen atom of one of the benzene
substituents of the porphyrin. In addition, contacts
between the phenyl group and three of the five methylene
spacer groups could be observed. Flexibility of the spacers
might enable the receptor to accommodate its cavity size
to that of the guest. However, in strapped porphyrin 20
self-inclusion takes place by the association of one of the
phenyl substituents of the porphyrin into the cavity of
the cavitand when dissolved in CD2Cl2.
F igu r e 2. Self-inclusion of 20 illustrated by its 1H NMR
spectra in CD2Cl2 (top) and in THF-d8 (bottom).
expressed by the doubled set of signals for the amide,
methine, and methylenedioxy bridges (Figure 2). The
plane of symmetry can only be positioned where it is
bisecting two distal methylenedioxy bridges. This is
the case when, on average, the oxygen atom of the
bound THF-d8 is pointing out of the cavity toward one of
the amides. Although the amides have an equal dis-
tance to the plane of symmetry, they are therefore
inequivalent, which is also reflected in the Ar-H sig-
nals of the cavitand; one of the two expected signals is
doubled giving three signals integrating in a 1:1:2
fashion.
This self-inclusion process is solvent dependent as can
be clearly seen in Figure 2. In the competitive solvent
THF-d8,20,21 the cavity is occupied by a solvent molecule
resulting in a 1H NMR spectrum with a C2-symmetry
(19) Different rotamers are formed. The carbonyl groups in the
linkers can be positioned inward versus outward and combinations
thereof.
(20) Solvent inclusion has been described by Cram: Cram, D. J .
Science 1988, 240, 760.
(21) From other aminomethyl-substituted cavitands prepared in our
laboratories, it is already known that, in CDCl3, THF is bound inside
the cavity with an association constant of ∼500 M-1. Unpublished
results.

Covalent Cavitand Zn(II)-Porphyrin Capsules
J . Org. Chem., Vol. 66, No. 11, 2001 4001
Because of the ring current of the porphyrin, in
CD2Cl2 the CH2 signals of the spacers are expected to
resonate at an upfield position;22 due to the self-inclusion
process, they have even shifted to negative δ values
(Figure 2). In THF-d8 these resonances have shifted far
downfield at positions where they are expected. The
combination of TOCSY and COSY spectra was used to
assign the signals of the methylene groups of the spacers
of 20 in CD2Cl2. The OCH2 group (δ -0.91) has only one
contact in the COSY spectrum with its neighboring
methylene group (δ -0.96), which has two contacts. The
other methylene substituents were assigned by TOCSY
NMR spectroscopy and are located at δ 0.14, 1.03, and
3.79.23 Knowing the positions, the COSY spectrum re-
veals the position of the methylene groups in the spacer.
The methylene group next to the amide is residing at δ
3.79, and it has a contact with its neighboring methylene
group located at δ 1.03. Consequently, the middle meth-
ylene group is located at δ 0.14.
Illustrative also are the changes in the splitting
patterns for the two different hydrogen atoms of the
pyrrole moieties of the porphyrin part of the receptor
when going from CD2Cl2 to THF-d8. Because of the
folding of the molecule in CD2Cl2, these two signals, and
many others, split up into multiple signals (Figure 2).
In the THF-d8 complex21 they become two signals which
reside as a broad singlet at δ 8.06 and as a multiplet at
around δ 8.67. The phenyl substituents now exhibit one
narrow multiplet.24
F igu r e 3. UV titration spectra showing the decrease of the
Soret band of 17 and the increase of the Soret band of the
complex upon picoline addition. The uncorrected data fit to a
calculated curve for
a
1:1 complexation with
.
a stability
constant of 2.3 × 105 M-1
Ta ble 1. Bin d in g Con sta n ts (×103 M-1) of th e
Com p lexa tion of N-Meth ylim id a zole a n d P yr id in e Gu ests
by Ca vita n d Zn (II)-P or p h yr in s 17-20 Deter m in ed by UV
Titr a tion Exp er im en ts in CHCl3. Th e Exp er im en ts Wer e
Ca r r ied Ou t in Du p lica te w ith a n Er r or Ma r gin betw een
3 a n d 10%
UV-Bin d in g Exp er im en ts. The complexation be-
havior of the cavitand Zn(II)-porphyrin receptors
17-20 toward N-methylimidazole and a series of pyridine
guests in CHCl3 was studied by UVtitrations. As an
illustration, Figure 3 shows the Soret band for cavitand-
capped Zn(II)-porphyrin 17 and of the complex in CHCl3
upon picoline addition. Both the decrease of the Soret
absorbance band of the free host at λ ) 424 nm and the
increase of the Soret absorbance band of the complex at
λ ) 434 nm are plotted as a function of the guest
concentration. Both curves gave, after correction for
dilution, a perfect fit to a 1:1 model (Kass ) 2.3 × 105 M-1).
The UV titration spectra, when corrected for dilution,
show the typical isosbestic point between the maximum
absorbance of the free host and that of the complex.
The results of the binding studies are summarized in
Table 1.25 For a few cases, the binding affinities of the
cavitand Zn(II)-porphyrins are in the same range (about
106 M-1) as those of the the best known receptors for
organic guests in organic solvents to date,6-9 demonstrat-
ing the strong potential of a cavitand as a hydrophobic
pocket. Some important trends can be seen from the
results. The strongest axial binding of N-methylimidazole
(22) Momenteau, M.; Mispelter, J .; Loock, B.; Bisagni, E. J . Chem.
Soc., Perkin Trans. 2 1983, 189.
(23) Many contacts are observed for the alkyl region in the COSY
NMR spectrum. TOCSY NMR shows the expected four contacts for
all spacer methylene groups in a straight line.
(24) When the sample was measured at 223 K, the hydrogens of
the porphyrin-pyrrole units appear as two doublets between δ 8.1 and
8.2 and as two doublets between δ 8.6 and 8.7. In addition, the doublet
originating from the methylene group between the amide and the
cavitand is doubled at 223 K, which clearly indicates the difference in
spatial freedom between both amide moieties in time and the symmetry
elements being lost.
(25) Pyridine, picoline, and N-methylimidazole are common guests
for studying the binding properties of porphyrin receptors, and some
additional guests were selected to demonstrate a clear guest to cavity-
size selection. The binding of N-methylimidazole is commonly accepted
as a model for oxygen binding capacities. See, e.g., ref 11.
and pyridine guests was found for cavitand-capped
Zn(II)-porphyrin 17, with the shortest distance between
the cavitand and the porphyrin increasing the shielding
effect. Furthermore, it has four spacers rigidifying the
structure to a receptor having a defined cavity. A large
difference between the smallest and the larger guests is
observed. The larger guests (nicotin, nicotinamides, and
p-phenylpyridine) bind at the outside of the receptor with

4002 J . Org. Chem., Vol. 66, No. 11, 2001
Middel et al.
a binding strength equal to or even lower26 than that to
TPP(Zn). The binding of the smaller guests, N-meth-
ylimidazole, pyridine, and picoline, is strongly influenced
by the capping effect of the cavitand, and they bind
strongest following the trend of highest electron density
on the donating nitrogen atom.
The longer and flexible spacers in 18 lead to a larger
but less defined cavity, and most guests bind inside the
receptor (except nicotin, not fitting in the cavity). The
longer spacer reduces the capping effect of the cavitand,
and the smaller guests bind typically weaker, although
in the same order as 17. For the pyridines the cavitand
capping effect is a factor27 of 6-32 (compared to TPP-
(Zn)), and the highest (94) value is that for N-methylimi-
dazole.
on the rigidity of the receptor, the number of spacers,
and the distance between the porphyrin and the cavitand.
Long flexible spacers result in a broader range of
potential guests. In the case of 18 and 20, a moderate
enhancement (10-90-fold) of the porphyrin binding
properties is observed due to self-inclusion. Short, rigid
spacers on the cavitand have a large impact on the
binding properties. Strapped porphyrin 19 shows large
binding enhancements for N-methylimidazole, picoline,
and nicotinamide (50-200-fold). The two additional rigid
spacers in capped porphyrin 17 increase the capping
effect to 700-fold in the case of N-methylimidazole.
Cavitand Zn(II)-porphyrin receptors 17 and 19 belong
to the best receptors for N-heterocycles reported to date.
The cavitand-strapped porphyrin 19 lacks two spacers
with respect to capped porphyrin 17. Consequently, the
shielding effect on the porphyrin will be reduced and,
more importantly, the flexibility of the system and the
cavitand-porphyrin distance are slightly increased. This
increase of distance allows p-phenylpyridine to be bound
inside the receptor. The two new windows enable the
sterically more demanding guests to bind inside. Strapped
porphyrin 19 binds nicotinamide28 by a factor 200 times
stronger (!) than that of TPP(Zn) and is the best of
receptors 17-20 for binding nicotinamide, p-phenylpy-
ridine, and isonicotinamide.
The elongation of the spacers in cavitand-strapped
porphyrin 20 results in a diminished cavitand capping
effect compared to 19. In 20 the flexibility of the spacers
allows the molecule to fold its spacers toward the interior
of the receptor, thereby minimizing its cavity size (vide
supra). This folding process promotes the self-inclusion
of a porphyrin phenyl moiety into the cavitand cavity.
The axial binding of guests in CHCl3, in this case, has to
compete with this process which is an additional energy
barrier to overcome. In general, the overall binding
affinities are less than those for 17-19, except for nicotin,
which probably has a cooperative hydrogen-bond interac-
tion with one of the spacer amides29 enhancing the
binding to receptor 20, thereby becoming the best recep-
tor for nicotin.
Exp er im en ta l Section
Gen er a l. Melting points are uncorrected. Mass positive
(FAB) spectra were obtained using m-nitrobenzyl alcohol as a
matrix. Column chromatography was performed using silica
gel 60 from Merck. All reactions were carried out under an
argon atmosphere, and solvents, if necessary, were purified
by standard procedures prior to use. The presence of solvents
1
in the analytical samples was confirmed by H NMR spectros-
copy.
NMR. All 1H (300 MHz) and13C NMR (63 MHz) spectra were
recorded in CDCl3 at ambient temperature (30 °C) unless
stated otherwise. The chemical shifts are expressed relative
to CHCl3 for 1H NMR (at δ 7.14) and 13C NMR (at δ 78.4).
NOESY,31 ROESY,32 TOCSY (MLEV 17),33 and COSY34 spectra
were performed using standard Varian pulse programs. The
TOCSY (MLEV 17) experiments were performed with mixing
times of 30 ms. The mixing times of the NOESY experiments
ranged from 10 to 90 ms. The mixing time of the ROESY
experiments consisted of a spin-lock pulse of 2 kHz field
strength with a duration of 30 ms, typically. All 2-D experi-
ments were collected using 2-D hypercomplex data35 and
Fourier transformed in the phase-sensitive mode after weight-
ing with shifted square sine bells or shifted Gaussian func-
tions. NMR data were processed by the standard VnmrS
software packages on the Unity 400 WB host computers (SUN
IPX and Sparc stations). Concentrations of the samples used
were typically in the 5 mM range. 6,18-Bis(aminomethyl)-12,-
24-(dimethyl)pentylcavitand14 1, 6,12,18,24-tetrakis(amino-
methyl)pentylcavitand13 2, and 6,12,18,24-tetrakis(chloroac-
etamido-N-methylene)pentylcavitand13 5 were synthesized
according to literature procedures reported by our group.
UV Titr a tion Exp er im en ts a n d Bin d in g Con sta n t
Det er m in a t ion . The concentrations of cavitand Zn(II)-
porphyrins used for the determination of the binding constants
by UV titrations were between 2 and 5 µM, and N-methylimi-
dazole and pyridine guests were added until more than 90%
of complex formation was observed. Binding constants were
determined by plotting the Soret absorbance band decrease
of the free hosts against the guest concentration, and also by
that of the Soret absorbance band increase of the complexes
against the guest concentrations. The experimental data were
fitted with the least-squares method to a theoretical curve
calculated with a 1:1 binding model. The experiments were
carried out in duplicate with an error margin between 3 and
10%.
The binding of N-methylimidazole by cavitand Zn(II)-
1
porphyrin 18 has been studied by H NMR spectroscopy
in CDCl3 to corroborate the result with the data obtained
with UV spectroscopy (vide supra). Characteristic for the
binding of N-methylimidazole30 (Kass ) 1.4 × 105 M-1
)
are the very large shifts for the signals of the guest owing
to the strong influence of the ring current of the porphy-
rin and its partial location in the cavity of the cavitand;
the methyl group shifts from δ 3.6 to -0.9. Only small
shifts are observed for signals originating from the
hydrogen atoms at the porphyrin and the OCH2 moiety
of the spacer.
Con clu sion s
Gen er a l Wor k u p P r oced u r es. P r oced u r e A. The reac-
tion was quenched with HCl (2 N, 100 mL), followed by
Our results clearly demonstrate that a cavitand is an
excellent cap for a porphyrin. The complexation depends
(31) (a) J eener, J .; Meier, B. H.; Ernst, R. R. J . Chem Phys. 1979,
71, 4546. (b) Neuhaus, D.; Williamson, M. In The Nuclear Overhauser
Effect in Structural and Conformational Analysis; VCH Publishers:
Cambridge, 1989.
(32) Bothner-By, A. A.; Stephens, R. L.; Lee, L.; Warren, C. D.;
J eanloz, R. W. J . Am. Chem. Soc. 1984, 106, 811.
(33) Bax, A.; Davis, D. J . Magn. Reson. 1985, 65, 355.
(34) Bax, A.; Freeman, R. J . Magn. Reson. 1981, 44, 542.
(35) States, D. J .; Haberkorn, R. A.; Ruben, D. J . J . Magn. Reson.
1982, 48, 286.
(26) One side of the porphyrin is blocked.
(27) The capping effect is expressed by comparison of the receptors
binding affinity to that of (Zn)TPP.
(28) On the basis of CPK molecular models, a cooperative hydrogen
bond is possible between one of the amides of the spacers and the
nicotinamide guest.
(29) Deviprasad, G. R.; D’Souza, F. Chem. Commun. 2000, 1915.
(30) From the literature it is known that 2-methylimidazole typically
binds stronger than N-methylimidazole. See, e.g., ref 7.

Covalent Cavitand Zn(II)-Porphyrin Capsules
J . Org. Chem., Vol. 66, No. 11, 2001 4003
washing the organic layer with water (100 mL) and 6 N NaOH
(50 mL), drying the organic layer over MgSO4, and evaporation
of the solvent. P r oced u r e B. The solvent was removed in
vacuo, and the residue was redissolved in CH2Cl2/H2O (200
mL/100 mL). The organic layer was dried over Na2SO4 and
concentrated to 10 mL (approximately), and the residue was
separated by column chromatography (SiO2, EtOAc). Elution
was performed with a gradient of MeOH (0, 5, 7, 10%) in
EtOAc. P r oced u r e C. The excess of pyrrole was removed in
vacuo, and the residue was taken up in CH2Cl2/0.1 N NaOH
(200 mL/50 mL). The organic layer was dried over Na2SO4 and
concentrated to 10 mL (approximately), and the residue was
separated by column chromatography (SiO2, CH2Cl2).
yielded 7 (2.91 g, 84%) as a white solid, mp 215-217 °C: 1H
NMR δ 0.91 (t, J ) 6.9 Hz, 12H), 1.28-1.45 (m, 24H), 1.91 (s,
6H), 2.13-2.27 (m, 8H), 4.37 (d, J ) 6.9 Hz, 4H), 4.50 (d, J )
7.3 Hz, 4H), 4.53 (s, 4H), 4.78 (t, J ) 8.1 Hz, 4H), 5.98 (d, J )
7.3 Hz, 4H), 6.90 (d, J ) 8.4 Hz, 2H), 6.98 (s, 2H), 7.12 (s,
2H), 7.18 (t, J ) 7.5 Hz, 4H), 7.57 (t, J ) 7.2 Hz, 2H), 7.78 (d,
J ) 7.5 Hz, 2H), 7.83 (t, J ) 5.7 Hz, 2H), 10.18 (s, 2H); 13C
NMR δ 9.9, 13.6, 20.3, 27.1, 29.6, 31.5, 33.3, 36.4, 59.8, 67.7,
99.0, 112.6, 116.5, 119.8, 121.6, 122.8, 123.4, 124.5, 133.4,
135.5, 136.9, 137.9, 152.9, 153.2, 157.2, 166.8, 170.5, 189.6;
FAB MS m/z 1249.5 [M + H + Na]+, calcd 1249.6. Anal. Calcd
for C74H86N2O14‚0.3CH2Cl2: C, 71.22; H, 6.97; N, 2.24. Found:
C, 71.05; H, 6.89; N, 2.31.
6,18-Bis(ch lor oa ceta m id o-N-m eth ylen e)-12,24-d im eth -
ylp en tylca vita n d (3). A solution of chloroacetyl chloride (1.05
g, 9.30 mmol) in CH2Cl2 (20 mL) was added dropwise to a
solution of 6,18-bis(aminomethyl)-12,24-(dimethyl)pentylcav-
itand 1 (1.68 g, 1.86 mmol) in a mixture of CH2Cl2 (150 mL)
and Et3N (15 mL) at -18 °C, whereupon stirring was contin-
ued overnight at rt. Workup procedure A yielded 3 (1.92 g,
98%) as a white solid, mp 100-102 °C: 1H NMR δ 0.92 (t, J
) 7.2 Hz, 12H), 1.30-1.50 (m, 24H), 1.95 (s, 6H), 2.10-2.30
(m, 8H), 4.02 (s, 4H), 4.34 (d, J ) 6.9 Hz, 4H), 4.40 (d, J ) 6.0
Hz, 4H), 4.76 (t, J ) 7.4 Hz, 4H), 5.94 (d, J ) 6.9 Hz, 4H),
6.96 (s, 2H), 7.02 (t, J ) 6.4 Hz, 2H), 7.11 (s, 2H); 13C NMR δ
10.5, 14.1, 22.7, 27.6, 30.9, 32.1, 35.5, 37.0, 42.7, 62.3, 99.5,
117.1, 120.6, 122.8, 124.1, 137.5, 138.6, 153.5, 153.5, 165.8;
6,18-Bis[5-(2-for m ylp h en oxy)p en t yla m id o-N-m et h yl-
en e]-12,24-d im eth ylp en tylca vita n d (8). A solution of sali-
cylaldehyde (1.17 g, 10.4 mmol) in CH3CN (5 mL) was added
to a suspension of 4 (3.0 g, 2.84 mmol) and K2CO3 (1.69 g, 12.2
mmol) in CH3CN (50 mL), whereupon the reaction mixture
was refluxed overnight. Workup procedure B and column
chromatography (SiO2, CH2Cl2/EtOAc 1:1.1, Rf ) 0.1) yielded
8 (2.91 g, 77%) as a white solid, mp 145-147 °C: 1H NMR δ
0.88 (t, J ) 6.7 Hz, 12H), 1.25-1.44 (m, 32H), 1.44-1.57 (m,
2H), 1.57-1.80 (m, 2H), 1.80-1.91 (m, 2H), 1.92 (s, 6H), 2.10-
2.25 (m, 8H), 4.01-4.10 (m, 8H), 4.20-4.32 (m, 8H), 4.74 (t, J
) 8.1 Hz, 4H), 5.92 (d, J ) 6.9 Hz, 4H), 6.15 (t, J ) 8.1 Hz,
4H), 6.90-7.10 (m, 8H), 7.11 (s, 2H), 7.46-7.53 (m, 2H), 7.78-
7.81 (m, 2H), 10.48 (s, 2H); 13C NMR δ 9.8, 13.5, 19.7, 22.1,
24.1, 24.6, 25.2, 25.9, 27.1, 27.8, 27.9, 28.0, 28.3, 29.5, 31.5,
31.7, 32.6, 33.7, 35.2, 35.9, 36.5, 44.2, 59.8, 67.6, 76.8, 98.7,
112.0, 116.7, 119.7, 120.0, 123.1, 123.5, 124.3, 127.7, 135.5,
137.0, 137.3, 138.0, 152.9, 153.0, 160.9, 162.0, 172.1, 189.2;
FAB MS m/z 1339.8 [M + H]+, calcd 1339.7. Anal. Calcd for
FAB m/z 1055.5 [M + H]+, calcd 1055.5. Anal. Calcd for C60H76
-
Cl2N2O10‚0.3CH2Cl2: C, 66.96; H, 7.14; N, 2.59. Found: C,
66.85; H, 7.02; N, 2.73.
6,18-Bis(5-b r om op e n t yla m id o-N -m e t h yle n e )-12,24-
d im eth ylp en tylca vita n d (4). A solution of 6-bromohexanoyl
chloride (1.99 g, 9.30 mmol) in CH2Cl2 (50 mL) was added
dropwise to a solution of 6,18-bis(aminomethyl)-12,24-(di-
methyl)pentylcavitand 1 (1.68 g, 1.86 mmol) in a mixture of
CH2Cl2 (150 mL) and Et3N (15 mL) at -10 °C, whereupon
stirring was continued for 2 h at rt. Workup procedure A was
followed by flash column chromatography (SiO2, CH2Cl2/EtOAc
7:3, Rf ) 0.8), yielding 4 (2.12 g, 91%) as a white solid, mp
143-145 °C: 1H NMR δ 0.95 (t, J ) 7.1 Hz, 12H), 1.25-1.45
(m, 16H), 1.45-1.55 (m, 4H), 1.55-2.00 (m, 12H), 1.96 (s, 6H),
2.12-2.22 (m, 4H), 2.29 (t, J ) 6.8 Hz, 4H), 3.47 (t, J ) 7.0
Hz, 4H), 4.35 (d, J ) 4.5 Hz, 4H), 4.37 (d, J ) 7.2 Hz, 4H),
4.74 (t, J ) 7.7 Hz, 4H), 5.91 (d, J ) 7.2 Hz, 4H), 6.23 (t, J )
5.2 Hz, 2H), 6.96 (s, 2H), 7.11 (s, 2H); 13C NMR δ 10.5, 14.2,
22.7, 23.5, 24.2, 26.1, 27.4, 27.6, 30.2, 32.3, 36.3, 44.7, 60.3,
99.3, 117.2, 120.1, 123.5, 123.9, 137.5, 138.5, 153.4, 153.6,
172.7; FAB MS m/z 1255.5 [M + H]+, calcd 1255.5. Anal. Calcd
C
82H102N2O14‚0.8CH2Cl2: C, 70.65; H, 7.42; N, 1.99. Found: C,
70.35; H, 7.61; N, 2.29.
6,12,18,24-Tet r a k is[(2-for m ylp h en oxy)a cet a m id o-N-
m eth ylen e]p en tylca vita n d (9). A solution of salicylaldehyde
(2,40 g, 21.4 mmol) in CH3CN (5 mL) was added to a
suspension of 6,12,18,24-tetrakis(chloroacetamidomethyl)-
pentylcavitand 5 (5.0 g, 3.96 mmol), NaI (0.1 g, catalytic), and
K2CO3 (5.0 g, mmol) in CH3CN (300 mL), whereupon the
reaction mixture was refluxed overnight. Workup procedure
B and elution with a gradient of EtOH (0, 10, 33%) in EtOAc
yielded 6 (3.87 g, 61%) (33% EtOH, Rf ) 0.3) as a red-brown
oil: 1H NMR δ 0.91 (t, J ) 6.6 Hz, 12H), 1.05-1.70 (m, 24H),
2.00-2.40 (m, 8H), 4.35 (d, J ) 6.1 Hz, 4H), 4.36 (d, J ) 7.4
Hz, 4H), 4.51 (s, 4H), 4.78 (t, J ) 7.3 Hz, 4H), 6.01 (d, J ) 7.4
Hz, 4H), 6.90 (d, J ) 8.0 Hz, 4H), 7.01 (s, 4H), 7.14 (t, J ) 4.8
Hz, 4H), 7.44-7.55 (m, 8H), 7.77 (d, J ) 6.4 Hz, 4H), 10.08 (s,
4H); 13C NMR δ 14.0, 22.5, 27.4, 30.0, 31.9, 33.6, 36.8, 42.4,
67.5, 99.7, 113.0, 119.8, 121.9, 123.2, 124.9, 133.0, 135.9, 138.1,
153.5, 157.8, 167.1, 189.9; FAB MS m/z 1602.7 [M + H + Na]+,
calcd for C92H100N4NaO20 1602.8.
6,12,18,24-Tetr a k is[5-(2-for m ylp h en oxy)p en tyla m id o-
N-m eth ylen e]p en tylca vita n d (10). A solution of salicylal-
dehyde (744 mg, 6.1 mmol) in CH3CN (5 mL) was added to a
suspension of 4 (1.0 g, 0.61 mmol) and K2CO3 (1.69 g, 12.2
mmol) in CH3CN (50 mL), whereupon the reaction mixture
was refluxed overnight. Workup procedure B and elution with
a gradient of MeOH (0, 5, 7, 10%) in EtOAc yielded 6 (960
mg, 87%) (10% MeOH, Rf ) 0.2) as a yellow-brown oil: 1H
NMR δ 0.93 (t, J ) 6.9 Hz, 12H), 1.20-1.50 (m, 32H), 1.50-
1.71 (m, 8H), 1.71-1.91 (m, 8H), 2.00-2.25 (m, 16H), 4.09 (t,
J ) 4.8 Hz, 8H), 4.27 (d, J ) 6.4 Hz, 4H), 4.38 (d, J ) 7.5 Hz,
4H), 4.75 (t, J ) 8.1 Hz, 4H), 5.95 (d, J ) 7.5 Hz, 4H), 5.94 (t,
J ) 5.1 Hz, 4H), 6.94-7.08 (m, 8H), 7.09 (s, 4H), 7.50-7.75
(m, 4H), 7.82 (d, J ) 7.2 Hz, 4H), 10.50 (s, 4H); 13C NMR δ
13.6, 22.1, 24.6, 25.9, 27.1, 31.5, 31.7, 33.6, 35.8, 36.4, 44.3,
67.7, 99.1, 112.0, 119.3, 120.0, 123.2, 124.3, 127.8, 135.5, 137.6,
153.1, 160.9, 172.0, 189.5; FAB MS m/z 1806.2 [M + H]+, calcd
1805.9. Anal. Calcd for C108H132N4O20‚1.7CH2Cl2: C, 67.55; H,
7.00; N, 2.87. Found: C, 67.33; H, 7.11; N, 3.25.
for
C68H92Br2N2O10‚0.3Et3N: C, 64.96; H, 7.38; N, 2.23.
Found: C, 64.68; H, 7.49; N, 2.55.
6,12,18,24-Tetr akis(5-br om open tylam ido-N-m eth ylen e)-
p en tylca vita n d (6). A solution of 6-bromohexanoyl chloride
(5.60 g, 26.17 mmol) in CH2Cl2 (50 mL) was added dropwise
to a solution of 6,12,18,24-tetrakis(aminomethyl)pentylcav-
itand 2 (2.77 g, 2.97 mmol) in a mixture of CH2Cl2 (100
mL) and Et3N (10 mL) at 0 °C, whereupon stirring was con-
tinued overnight at rt. Workup procedure A was followed by
flash column chromatography (SiO2, EtOAc/MeOH 4:1, Rf )
0.3). Addition of hexane to a CH2Cl2 solution yielded 4 (4.26
g, 88%) as a colorless oil: 1H NMR δ 0.95 (t, J ) 6.7 Hz,
12H), 1.20-1.51 (m, 32H), 1.51-1.69 (m, 8H), 1.69-1.90 (m,
8H), 2.05-2.30 (m, 16H), 3.52 (t, J ) 6.2 Hz, 8H), 4.31 (d,
J ) 4.5 Hz, 4H), 4.38 (d, J ) 6.5 Hz, 4H), 4.72 (t, J ) 8.6 Hz,
4H), 5.92 (d, J ) 7.2 Hz, 4H), 5.93 (t, J ) 5.2 Hz, 4H), 7.04 (s,
4H); 13C NMR δ 13.6, 22.1, 24.2, 25.9, 27.1, 31.5, 31.7, 33.6,
35.7, 36.4, 44.3, 52.7, 99.1, 119.3, 123.2, 137.6, 153.1, 172.0;
FAB MS m/z 1637.5 [M + H]+, calcd for C80H112Br4N4O12
1637.5.
6,18-Bis[(2-for m ylp h en oxy)a cet a m id o-N-m et h ylen e]-
12,24-d im eth ylp en tylca vita n d (7). A solution of salicylal-
dehyde (1.39 g, 11.4 mmol) in CH3CN (10 mL) was added to a
suspension of 3 (3.0 g, 2.84 mmol), K2CO3 (1.69 g, 12.2 mmol),
and NaI (100 mg, catalyst) in CH3CN (100 mL), whereupon
the reaction mixture was refluxed overnight. Workup proce-
dure B and column chromatography (SiO2, EtOAc, Rf ) 0.3)
6,18-B is [(2-p y r r o ly lm e t h y lp h e n o x y )a c e t a m id o -N -
m eth ylen e]-12,24-d im eth ylp en tylca vita n d (11). To a de-
gassed solution of dialdehyde 7 (150 mg, 0.12 mmol) in pyrrole
(40 mL) was added TFA (0.4 mL, catalytic). Stirring for 30

4004 J . Org. Chem., Vol. 66, No. 11, 2001
Middel et al.
min at rt, followed by workup procedure C and column
chromatography (SiO2, CH2Cl2/EtOAc 1:1, Rf ) 0.2) yielded
11 (161 mg, 90%) as a gray-blue heat- and light-sensitive solid,
decomposing upon standing (!): 1H NMR δ 0.94 (t, J ) 7.2
Hz, 12H), 1.25-1.50 (m, 24H), 1.82 (s, 6H), 2.10-2.35 (m, 8H),
4.09 (d, J ) 7.3 Hz, 4H), 4.20 (d, J ) 5.1 Hz, 4H), 4.26 (s, 4H),
4.74 (t, J ) 8.4 Hz, 4H), 5.55 (brs, 2H), 5.63 (d, J ) 7.5 Hz,
2H), 5.95-6.05 (m, 6H), 6.65 (d, J ) 8.1 Hz, 2H), 7.14 (s, 2H),
7.21 (s, 2H), 7.21-7.25 (m, 4H), 8.34 (brs, 2H); 13C NMR
(CD2Cl2) δ 9.0, 13.3, 13.4, 22.1, 27.1, 29.7, 31.5, 32.9, 36.6, 38.2,
59.7, 66.3, 98.4, 106.0, 107.5, 111.1, 116.4, 117.5, 119.8, 121.5,
122.3, 123.3, 127.8, 128.9, 130.4, 130.6, 137.4, 137.6, 152.9,
153.1, 153.6, 166.8; FAB MS m/z 1458.7 [M + H]+, calcd
1458.8. Anal. Calcd for C90H102N6O12: C, 74.05; H, 7.04; N,
5.76. Found: C, 74.32; H, 6.92; N, 5.67.
6,18-Bis[5-(2-p yr r olylm eth ylp h en oxy)p en tyla m id o-N-
m eth ylen e]-12,24-d im eth ylp en tylca vita n d (12). To a de-
gassed solution of dialdehyde 8 (1.0 g, 0.75 mmol) in pyrrole
(65 mL) was added TFA (0.1 mL, catalytic). Stirring for 30
min at rt followed by workup procedure C and column
chromatography (SiO2, CH2Cl2/EtOAc 5:2, Rf ) 0.3) yielded
12 (620 mg, 53%) as an off-white heat- and light-sensitive solid,
decomposing upon standing (!): 1H NMR δ 0.91 (t, J ) 7.2
Hz, 12H), 1.25-1.50 (m, 32H), 1.52-1.75 (m, 4H), 1.78 (s, 6H),
2.10-2.35 (m, 12H), 3.93 (t, J ) 6.3 Hz, 4H), 4.15-4.30 (m,
8H), 4.74 (t, J ) 8.1 Hz, 4H), 5.80 (s, 2H), 5.84 (d, J ) 7.1 Hz,
4H), 5.85 (brs, 2H), 6.06-6.10 (m, 2H), 6.61-6.64 (m, 2H),
6.83-6.90 (m, 4H), 6.95 (s, 2H), 7.06-7.10 (m, 2H), 7.09 (s,
2H), 7.14-7.22 (m, 2H), 8.46 (brs, 2H); 13C NMR δ 14.1, 14.2,
22.7, 25.1, 25.6, 27.6, 28.8, 30.1, 32.1, 32.2, 34.2, 36.3, 36.8,
37.0, 37.8, 67.8, 99.1, 106.5, 108.0, 112.0, 116.6, 117.2, 120.2,
120.8, 123.5, 124.1, 127.9, 129.5, 131.3, 132.9, 137.6, 138.6,
153.4, 153.5, 156.0, 172.9; FAB MS m/z 1571.8 [M + H]+, calcd
1571.9. Anal. Calcd for C98H118N6O12: C, 74.88; H, 7.57; N,
5.35. Found: C, 74.43; H, 7.42; N, 5.57.
Gen er a l P r oced u r e for th e In ser tion of Zn (II). The
reaction mixture of the cavitand (2H)-porphyrin synthesis was
evaporated to dryness and redissolved in CH2Cl2 (100 mL) and
aqueous NaHCO3 (50 mL). The organic layer was dried over
Na2SO4, and the residue was separated by column chroma-
tography (SiO2, CH2Cl2/Et3N, 99:1). The strongly colored
porphyrin bands of the cavitand (2H)-porphyrins 13-16,
containing non-porphyrin impurities, were isolated by elution
with a gradient of MeOH (1 up to 10%) in CH2Cl2/Et3N (99:1)
and evaporated to dryness. The residues were redissolved in
CHCl3/MeOH (1:1) and refluxed overnight with a large excess
(approximately 50 equiv) of Zn(OAc)2. The reaction mixture
was evaporated to dryness and redissolved in CH2Cl2 (50 mL)
and H2O (20 mL). The organic layer was dried over Na2SO4
and evaporated to dryness. This residue was redissolved in
the eluent needed for column chromatography.
Ca vit a n d -Ca p p ed Zn (II)-P or p h yr in 17. A mixture of
tetraaldehyde 9 (655 mg, 0.41 mmol) and pyrrole (111 mg, 1.66
mmol) in propionic acid (200 mL) was refluxed overnight. For
the workup of 13, 2% MeOH was used in the eluent. The
fraction with Rf ) 0.4-0.7 was again separated by column
chromatography (SiO2, Et2O/CHCl3 2:5). Zn(II) was inserted
via the general procedure. Final purification by preparative
TLC (SiO2, Et2O/CHCl3 2:5, Rf ) 0.15) gave 17 (7.0 mg, 0.9%)
as a pinkish-purple solid, mp 209-211 °C (dec). Compound
13 consisting of at least two rotamers/isomers: 1H NMR δ
-2.72 (s, 1H), -2.80 (s, 1H). Compound 17: 1H NMR (400
MHz) δ 0.78 (t, J ) 7.0 Hz, 6H), 0.93 (t, J ) 7.0 Hz, 6H),
1.05-1.50 (m, 16H), 1.60-1.85 (m, 8H), 3.29 (s, 2H), 3.33 (s,
4H), 3.34 (s, 2H), 3.50-3.80 (m, 8H), 4.18 (d, J ) 7.2 Hz, 4H),
4.62-4.78 (m, 4H), 4.91 (brs, 1H), 5.16 (d, J ) 7.2 Hz, 4H),
5.90-5.98 (brs, 1H), 6.43 (t, J ) 4.8 Hz, 1H), 6.51 (brs, 1H),
7.02 (s, 1H), 7.14-7.30 (m, 7H), 7.40-7.76 (m, 8H), 8.08 (d, J
) 8.0 Hz, 4H), 8.60-8.68 (m, 8H); 13C NMR δ 12.8, 16.9, 26.1,
28.9, 31.5, 33.2, 30.1, 32.1, 32.2, 33.8, 35.5, 40.5, 47.9, 67.8,
99.1, 104.6, 104.9, 118.0, 121.4, 122.4, 123.6, 120.8, 124.0,
124.6, 128.1, 129.6, 130.6, 134.4, 134.7, 134.9, 138.3, 141.8,
142.0, 153.8, 153.9, 157.4, 163.0; FAB MS m/z 1836.0 [M +
H]+, calcd 1836.5. Anal. Calcd for C108H104N8O16Zn: C, 70.67;
H, 5.71; N, 6.10. Found: C, 70.30; H, 6.02; N, 5.99.
Ca vita n d -Ca p p ed Zn (II)-P or p h yr in 18. A solution of
tetraaldehyde 10 (800 mg, 0.443 mmol) in freshly distilled CH2-
Cl2 (500 mL) was degassed at -40 °C and, subsequently,
saturated with argon. The solution was allowed to warm to
rt, whereupon a solution of freshly distilled pyrrole (119 mg,
1.80 mmol) in CH2Cl2 (2 mL) was added via a septum followed
by the addition of a solution of freshly distilled BF3‚OEt2 (252
mg, 1.80 mmol) in CH2Cl2 (2 mL). After the solution was
stirred for 45 min, p-chloroanil (500 mg, excess) was added,
and the reaction mixture was refluxed for 1 h. For the workup
procedure, 7% MeOH in CH2Cl2 was used for column chroma-
tography to obtain (2H)-porphyrin 14. Upon the introduction
of Zn(II) via the general procedure, the reaction mixture was
separated by column chromatography (SiO2, CH2Cl2/EtOAc
1:1, Rf ) 0.2), yielding 18 (53 mg, 6%) as a purple solid, mp
208-210 °C (dec). Compound 14: 1H NMR δ -2.88 (s, 2H).
Compound 18: 1H NMR (400 MHz, THF-d8) δ 0.60-0.63 (m,
8H), 0.63-0.92 (m, 40H), 1.09-1.60 (m, 24H), 1.72-2.15 (m,
16H), 3.74 (t, J ) 6.4 Hz, 8H), 3.90-3.95 (m, 12H), 4.53 (t, J
) 8.4 Hz, 4H), 5.51 (d, J ) 7.2 Hz, 4H), 6.71 (t, J ) 6.0 Hz,
4H), 6.97 (s, 4H), 7.17-7.27 (m, 8H), 7.56-7.70 (m, 4H), 7.81-
7.88 (m, 4H), 8.59 (s, 8H); 13C NMR δ 16.8, 26.0, 28.8, 31.1,
32.8, 33.1, 33.9, 35.4, 37.2, 38.4, 40.4, 72.9, 76.2, 104.3, 116.4,
119.5, 122.6, 128.6, 132.4, 134.1, 137.0, 139.3, 141.4, 153.7,
157.6, 163.3, 174.6; FAB MS m/z 2058.3 [M + H]+, calcd for
C
124H136N8O16Zn 2057.9.
Ca vita n d -Str a p p ed Zn (II)-P or p h yr in 19. A solution of
dipyrromethane 11 (0.54 g, 0.37 mmol) and benzaldehyde (79
mg, 0.74 mmol) in freshly distilled CH2Cl2 (200 mL) was
degassed at -40 °C and, subsequently, saturated with argon.
The solution was allowed to warm to rt and TFA (0.2 mL,
catalytic) was added, whereupon the reaction mixture was
stirred for 45 min. Subsequently, p-chloroanil (500 mg, excess)
was added and the reaction mixture was refluxed for 1 h. For
the workup procedure, 2% MeOH in CH2Cl2 was used for
column chromatography to obtain (2H)-porphyrin 15. Zn(II)
was inserted via the general procedure and followed by column
chromatography first using CH2Cl2 as the eluent to remove
some impurities. Strapped porphyrin 19 (17 mg, 3%) was
isolated (CH2Cl2/EtOAc 1:1, Rf ) 0.5) as a purple solid, mp
1
152-154 °C (dec). Compound 15: H NMR δ -2.68 (brs, 2H).
Compound 19: 1H NMR (400 MHz, CDCl3/THF-d8 ) 1:1) δ
0.85-1.10 (m, 12H), 1.10-1.80 (m, 24H), 2.00 (s, 3H), 2.03 (s,
3H), 2.12-2.16 (m, 8H), 3.06 (d, J ) 6.9 Hz, 4H), 3.55-3.95
(m, 4H), 4.00-4.20 (m, 4H), 4.72 (m), 5.14 (d, J ) 6.9 Hz, 4H),
5.52-5.56 (brs, 1H), 5.93-5.97 (brs, 1H), 6.48 (s, 2H), 6.75 (s,
2H), 7.32-7.35 (m, 4H), 7.40-7.50 (m, 6H), 7.62 (d, J ) 7.1
Hz, 2H), 7.65 (d, J ) 7.1 Hz, 2H), 7.68-7.80 (m, 8H), 8.64-
8.90 (m, 8H); 13C NMR δ 12.8, 16.9, 26.1, 28.9, 31.5, 33.2, 33.8,
35.5, 40.4, 40.5, 40.5, 47.9, 67.8, 102.2, 102.5, 115.8, 120.5,
121.0, 122.2, 123.7, 124.0, 127.8, 129.9, 130.4, 132.3, 134.2,
134.4, 134.5, 137.9, 139.0, 141.1, 142.2, 147.7, 153.8, 153.8,
154.2, 157.6, 157.8, 157.9, 162.7, 163.6, 174.2; FAB MS m/z
1501.2 [M]-, calcd 1501.2. Anal. Calcd for C104H102N6O12Zn‚
1.0THF-d8:36 C, 73.14; H, 5.80; N, 4.74. Found: C, 72.95; H,
5.64; N, 4.39.
Ca vita n d -Str a p p ed Zn (II)-P or p h yr in 20. A solution of
dipyrromethane 12 (0.81 g, 0.61 mmol) and benzaldehyde (128
mg, 1.22 mmol) in freshly distilled CH2Cl2 (200 mL) was
degassed at -40 °C and, subsequently, saturated with argon.
The solution was allowed to warm to rt and freshly distilled
BF3‚OEt2 (0.1 mL, catalytic) was added, whereupon the reac-
tion mixture was stirred for 3 h. Subsequently, p-chloroanil
(500 mg, excess) was added and the reaction mixture was re-
fluxed for 1 h. For the workup procedure, 2% MeOH in CH2Cl2
was used for column chromatography to obtain (2H)-porphyrin
16. Zn(II) was inserted via the general procedure, and the
reaction mixture was separated by column chromatography
using (CH2Cl2/EtOAc 1:1, Rf ) 0.5) as the eluent. Strapped
porphyrin 20 (55 mg, 5%) was isolated as a purple solid, mp
1
159-161 °C (dec). Compound 16: H NMR δ -2.68 (brs, 2H).
(36) The sample used for 13C NMR was evaporated to dryness and
used for elemental analysis. The cavity is probably occupied by a
molecule of THF-d8.

Covalent Cavitand Zn(II)-Porphyrin Capsules
J . Org. Chem., Vol. 66, No. 11, 2001 4005
1
Compound 20: H NMR (400 MHz, THF-d8) δ 0.43-0.50 (m,
38.5, 39.3, 40.6, 47.9, 48.4, 72.0, 102.3, 102.5, 118.8, 120.2,
120.9, 122.0, 122.5, 123.3, 123.8, 123.9, 127.7, 128.4, 128.7,
129.6, 130.5, 132.7, 134.5, 134.5, 138.0, 139.1, 139.9, 141.3,
141.8, 147.5, 156.6, 157.0, 158.5, 174.2; FAB MS m/z 1825.8
2H), 0.56-0.61 (m, 2H), 0.76-0.82 (m, 12H), 0.88 (t, J ) 7.2
Hz, 2H), 0.98 (t, J ) 7.2 Hz, 2H), 1.04-1.16 (m, 2H), 1.19-
1.40 (m, 24H), 1.44-1.60 (m, 4H), 1.75 (s, 6H), 1.85-1.95 (m,
2H), 2.00-2.30 (m, 8H), 3.37 (t, J ) 6.8 Hz, 2H), 3.47 (d, J )
7.2 Hz, 2H), 3.80 (t, J ) 6.8 Hz, 2H), 3.88 (d, J ) 7.2 Hz, 2H),
4.07-4.09 (m, 4H), 4.60 (t, J ) 8.0 Hz, 2H), 4.68 (t, J ) 8.0
Hz, 2H), 5.37 (d, J ) 7.2 Hz, 2H), 5.66 (d, J ) 7.2 Hz, 2H),
5.82 (brs, 1H), 6.50 (brs, 1H), 6.95 (s, 2H), 7.02 (s, 1H), 7.07
(s, 1H), 7.18 (t, J ) 7.6 Hz, 2H), 7.26 (d, J ) 8.0 Hz, 2H), 7.37-
7.63 (m, 12H), 7.84 (d, J ) 7.6 Hz, 2H), 8.06 (brs, 4H), 8.65-
8.67 (m, 4H); 13C NMR (63 MHz, THF-d8) δ 12.8, 16.9, 26.1,
28.4, 30.1, 31.3, 32.1, 33.0, 33.1, 33.8, 35.5, 36.0, 36.1, 36.8,
[M + H + Na]+, calcd 1825.8. Anal. Calcd for C112H118N6O12
-
Zn‚0.8MeOH: C, 73.99; H, 6.67 N, 4.59. Found: C, 73.85; H,
6.37; N, 4.32.
Ack n ow led gm en t. We are grateful to the Council
for Chemical Sciences of The Netherlands Organization
for Scientific Research (CW-NWO) for financial support.
J O010107K